These investigations are directed toward identifying the factors influencing protein-sparing therapy during hypocaloric feeding. These factors include: 1) nitrogen intake, 2) availability of non-protein calories, 3) metabolic rate, 4) nutritional status; i.e., protein status, 5) presence of sepsis, 6) development of ketone body adaptation and fat mobilization, 7) time. Further, the criteria of efficacy have been extended beyond nitrogen balance to assessment of visceral protein synthesis. Particularly valuable indices include albumin synthesis rate, serum transferrin and delayed hypersensitivity reaction to common skin antigens (mumps, candida, SKSD). The functional redistribution of body protein, primarily muscle, is dependent upon the status of that protein mass. Malnutrition and infection exaggerate the stress of injury, exacerbating morbidity. The nutritional therapy indicated by surgical trauma is one which will take advantage of the intrinsic teleological mechanisms that have evolved to utilize the endogenous sources of protein and energy. It is not sufficient to speak of protein-sparing in terms of nitrogen balance: a distinction must be made as to what protein is being spared and for what purpose. The reallotment of protein from muscle to viscera while using fat or fuel best meets the host's immediate end, survival. Given the limitations of osmotic tolerance to I.V. feeding, the provision of near-isotonic amino acid solution with electrolytes can substantially influence nitrogen metabolism after surgical injury and enhance protein-sparing in tissue key to survival.